ARC-Net Research Centre, University and Hospital Trust of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, Piastra Odontoiatrica (II floor), Verona, Italy.
Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy.
Virchows Arch. 2018 Dec;473(6):709-717. doi: 10.1007/s00428-018-2450-x. Epub 2018 Sep 16.
Small intestine neuroendocrine tumors (SI-NETs) represent the most common histotype among small intestine neoplasms, and metastatic disease is usually present at diagnosis. A retrospective series of 52 sporadic primary surgically resected SI-NETs, which were metastatic at diagnosis, was analyzed by high-coverage target sequencing (HCTS) for the mutational status of 57 genes and copy number status of 40 genes selected from recently published genome sequencing data. Seven genes were found to be recurrently mutated: CDKN1B (9.6%), APC and CDKN2C (each 7.7%), BRAF, KRAS, PIK3CA, and TP53 (each 3.8%). Copy number analysis showed frequent allelic loss of 4 genes located on chromosome 18 (BCL2, CDH19, DCC, and SMAD4) in 23/52 (44.2%) and losses on chromosomes 11 (38%) and 16 (15%). Other recurrent copy number variations were gains for genes located on chromosomes 4 (31%), 5 (27%), 14 (36%), and 20 (20%). Univariate survival analysis showed that SRC gene copy number gains were associated with a poorer prognosis (p = 0.047). Recurrent copy number variations are important events in SI-NET and SRC may represent a novel prognostic biomarker for this tumor type.
小肠类癌肿瘤（SI-NETs）是小肠肿瘤中最常见的组织学类型，且通常在诊断时已发生转移。本研究通过高覆盖度靶向测序（HCTS）对 52 例经手术切除的、初诊时已转移的散发性原发性 SI-NET 进行了分析，检测了 57 个基因的突变状态和 40 个基因的拷贝数状态，这些基因是从最近发表的基因组测序数据中选择的。结果发现 7 个基因存在高频突变：CDKN1B（9.6%）、APC 和 CDKN2C（各 7.7%）、BRAF、KRAS、PIK3CA 和 TP53（各 3.8%）。拷贝数分析显示，23/52（44.2%）例肿瘤中位于 18 号染色体上的 4 个基因（BCL2、CDH19、DCC 和 SMAD4）存在等位基因缺失，以及 11 号染色体（38%）和 16 号染色体（15%）缺失。其他高频拷贝数变异包括 4 号染色体（31%）、5 号染色体（27%）、14 号染色体（36%）和 20 号染色体（20%）上基因的增益。单因素生存分析显示 SRC 基因拷贝数增益与预后不良相关（p=0.047）。复发性拷贝数变化是 SI-NET 的重要事件，SRC 可能代表该肿瘤类型的一种新的预后生物标志物。
